Our main research objective is to investigate the cellular basis of associative, discriminative conditioning in a simplified circuit in the mammalian brain in which neural changes can be related to mediation of conditioning. Changes in neural activity and excitability supporting discrimination of a conditioned stimulus from another auditory stimulus will be investigated in neurons of subcortical auditory areas in relation to slowly and rapidly acquired eyeblink conditioning. The short (8-12 ms) latency of the CR is indicative of a reduced throughput circuitry which facilitates the necessary anatomical, electrophysiological and behavioral analyses. Other aims are: 1. To identify the membrane properties of intracellularly studied units that support activity and excitability changes related to conditioning. 2. To distinguish different types of involved cells, their local circuities, and their more distant axonal projections by intracellular injection of marking agents. 3. To study effects of rapidly acting putative neurotransmitters, their blocking agents, and their possible intracellular messengers on subcortical neurons shown to be active in supporting discriminative conditioning. The results should provide significant information about neural mechanisms and pathways in mammals that mediate associative, discriminative conditioning and related aspects of short and long term memory. Further information will be obtained about the role of subcortical neurons in accelerating rates of acquisition of this conditioned response. Present understanding of learning and related phenomena is limited by a lack of specific knowledge. Much of the current medical practice in the areas of 1) rehabilitation of stroke victims, 2) behavioral psychotherapy, and 3) treatment of mental retardation and memory disorders is similarly limited. New knowledge could potentially be applied to these human health care needs.